3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-D-glucopyranosyl 4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate | 1001406-34-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-D-glucopyranosyl 4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate
• 英文别名: 3,4,6-tri-O-benzyl-1-[4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate]-2-deoxy-2-fluoro-α,β-D-glucopyranose
• CAS: 1001406-34-3
• 化学式: C₄₁H₄₆Cl₂FNO₆
• 分子量: 738.724
• InChiKey: FTQIWFCKLVXENK-LMKVRZHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.29
• 重原子数：
  51.0
• 可旋转键数：
  20.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  66.46
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-D-glucopyranosyl 4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate 在 palladium 10% on activated carbon 甲酸铵 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.5h， 生成 2-deoxy-2-fluoro-β-D-glucopyranosyl 4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate 、 2-deoxy-2-fluoro-α-D-glucopyranosyl 4-{4-[bis(2-chloroethyl)amino]phenyl}butyrate
  参考文献：
  名称：

  Conjugates of 2-fluoro-2-deoxy-glucose and their uses as anti cancer agents

  摘要：

  本发明涉及一般式（I）的化合物：其中：- R1、R2和R3分别独立地表示氢原子或可选择取代的较低烷基，（C1-C7）酰基团或苄基，- R4是可选择取代和/或中断的碳氢链，- X和Y分别独立地从-NH-，-NR'-，-CO-，-NH（CO）-，-NH（CO）NH-，-NR'（CO）-，-O（CO）NH-，-O（CO）NR'-，-（CO）NH-，-（CO）NR'-，-NH（CO）（R"）NH（CO）-，-（CO）NH（R"（CO）NH-，-O-，-（CO）O-，-NH（CO）O-，-SC（O）NH-，-NHSO2-，-NR'SO2-和-O（CO）-中选择，并且最好彼此不同，其中R'是可选择取代的较低烷基团，R"是（C1-C3）烷基，- Z基团代表抗肿瘤剂，- n表示0或1，- 及其药用盐。还涉及将这些化合物用作抗癌剂。

  公开号：

  EP1881000A1

文献信息

• Synthesis and cytotoxic properties of new fluorodeoxyglucose-coupled chlorambucil derivatives
  作者：Bastien Reux、Valérie Weber、Marie-Josephe Galmier、Michèle Borel、Michel Madesclaire、Jean-Claude Madelmont、Eric Debiton、Pascal Coudert

  DOI：10.1016/j.bmc.2008.03.038

  日期：2008.5

  Frequently used in the treatment of malignant cells, alkylating agents, like most anticancer substances, produce adverse side effects caused by the toxicity of the agents toward normal tissues and lose efficiency through poor distribution to target sites. Our approach to developing more selective drugs with low systemic toxicity is based on the premise that the body distribution and cell uptake of a drug can be altered by attaching a neoplastic cell-specific uptake enhancer, such as 2-fluoro-2-deoxyglucose (FDG), the radiotracer most frequently used in PET for tumor imaging. Two properties of deoxyglucose, namely preferential accumulation in neoplastic cells and inhibition of glycolysis, underpin this targeting approach. Here, we report the synthesis of 19 new chlorambucil glycoconjugates in which the alkylating drug is attached to the C-1 position of FDG, directly or via different linkages. This set of compounds was evaluated for in vitro cytotoxicity against different human normal and tumor cell lines. There was a significant improvement in the in vitro cytotoxicity of peracetylated glucoconjugates compared with the free substance. Four compounds were finally selected for further in vivo studies owing to their lack of oxidative stress-inducing properties. (c) 2008 Elsevier Ltd. All rights reserved.